EP0227173A2 - Procédé pour la détection des agents liants spécifiques et leurs substances liables correspondantes - Google Patents
Procédé pour la détection des agents liants spécifiques et leurs substances liables correspondantes Download PDFInfo
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- EP0227173A2 EP0227173A2 EP86202231A EP86202231A EP0227173A2 EP 0227173 A2 EP0227173 A2 EP 0227173A2 EP 86202231 A EP86202231 A EP 86202231A EP 86202231 A EP86202231 A EP 86202231A EP 0227173 A2 EP0227173 A2 EP 0227173A2
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- European Patent Office
- Prior art keywords
- latex particles
- colourable
- coloured
- bindable
- latex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/80—Fluorescent dyes, e.g. rhodamine
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/805—Optical property
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/807—Apparatus included in process claim, e.g. physical support structures
- Y10S436/808—Automated or kit
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/823—Immunogenic carrier or carrier per se
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2991—Coated
Definitions
- the method according to the present invention differs from the previous methods essentially by the fact that as a marker to detect or determine the complex formed between a specific binding protein and the corresponding bindable substances there are used latex particles which can be detected visually due to their capability to absorb light in the visual spectrum, or to emit light after irradiation.
- the former detection is based on colour, the latter on fluorescence.
- the present invention is concerned with a method of qualitatively or quantitatively determining a component of a complex formed between at least one specific binding agent, which preferably is a specific binding protein, and its corresponding bindable substance.
- Said method comprises labelling at least one component of said complex with a marker which is easier to determine than the complex itself, whereby the marker used consists of latex particles which can be detected visually due to their capability to absorb light in the visual spectrum, or to emit light after irradiation, the former detection being based on colour, the latter on fluorescence.
- the marker consists of coloured or colourable latex particles and the determination is based on the colour characteristics of the latex particles as such or, in the instance that colourable latex particles are used, on the colour characteristics of the coloured particles derived therefrom.
- the colour, respectively fluorescence signal is, if necessary after development, easily detected and optionally quantified.
- the method is essentially based on the fact that the specific binding agents or any agents bindable thereby, when brought into contact with the latex particles under appropriate conditions, do strongly adsorb thereon without loosing their affinity for their binding or bindable counterpart and that the signal density of the particles is sufficient to allow the detection and/or quantification of small concentrations and amounts.
- the thus labelled specific binding agents or bindable agents when allowed to interact with their counterparts will attach their label to the complex formed during the interaction and consequently the detection thereof can be easily performed making use of the optical properties of the latex particles, especially of their fluorescence and colour characteristics.
- the latex particles for use in the method according to the invention are meant to include any aqueous dispersion of synthetic homopolymers or copolymers containing moieties which can, if necessary after development, absorb light in the visual spectrum or emit light after irradiation.
- the said moieties can either be covalently bound to the polymers, e.g. the polymers comprise recurring units carrying such a moiety, or can be incorporated in the latex particles, e.g. when a molecule containing such a moiety is solvatated in the latex particle.
- the latex particles for use in the method according to the present invention are detectable on basis of their colour.
- Particularly preferred latex particles are those wherein the colour is due to recurring units carrying a light absorbing moiety or which can be chemically converted into such moiety, e.g. by the oxidative coupling of the latter with an aromatic primary amino compound to form a dye.
- coloured and colourable latexes are well-known in the art and comprise, for example, homo- or copolymers of metacrylamide units wherein the amide nitrogen atom is chemically bound to a coloured or colourable residue.
- metacrylamide monomers carrying a coloured residue and their preparation will be found e.g. in Shih, Yen Jer, "COLORED LATEXES: PREPARATION, CHARACTERIZATION AND APPLICATION", Lehigh University (l98l).
- a typical preparation comprises an emulsion polymerization of styrene monomer, seeded polymerization with reactive halogenated monomer, amination with N -methylaniline and a coupling reaction with a diazonium salt, e.g. a benzenesulfonate diazonium salt.
- a diazonium salt e.g. a benzenesulfonate diazonium salt.
- the coloured latexes may contain different chromophores, such as, for example, anthraquinone residues.
- Colourable latexes which can be used in accordance with the present invention include, e.g., the various types of colour complex latexes used in photographic colour film.
- homo- or co-polymers comprising recurring units carrying a moiety capable of oxidatively coupling with an aromatic primary amino compound to form a dye.
- Examples of monomeric colour couplers used according to the present invention can be found e.g. in the Belgian Patent Specifications 584,494, 602,5l6 and 669,97l, in the United Kingdom Patent Specifications 967,503, l,l30,58l; l,247,688; l,269,355; and in the United States Patent Specification 3,356,686.
- monomeric colour couplers are: 2-methylsulfonylamino-5-methacrylaminophenol; 2-methylsulfonylamino-4-chloro-5-methacrylaminophenol; 2-phenylsulfonylamino-5-methacrylaminophenol; 2-(4-chlorophenyl)sulfonylamino-5-methacrylaminophenol; 2-(4-sec.butylphenyl)sulfonylamino-5-methacrylaminophenol; 2-ethoxycarbonylamino-5-methacrylaminophenol; 2-n.butylureido-5-methacrylaminophenol; 2-benzoylamino-5-methacrylaminophenol; 2- o -methylbenzoylamino-5-methacrylaminophenol; 2-acetylamino-5-methacrylaminophenol; 2- p -methoxybenzoylamino-5-methacrylamino
- polymeric compounds e.g. polymeric couplers for use according to the present invention
- equivalent molecular weight is understood the number of grams of polymer containing l mole of polymerized monomeric compound with the chemically reactive moiety, e.g. monomeric coupler. It can be compared with the molecular weight of the non-polymeric classical non-migratory chemically reactive compound, e.g. coupler.
- the equivalent molecular weight of polymeric latex compounds according to the invention can vary within very wide limits, preferable from 200 to 2000.
- the latexes used in the present invention can be prepared by emulsion polymerization using a polymerization initiator as described e.g. in the United States Patent Specification 3,926,436 and United Kingdom Patent Specification No. l,l30,58l.
- polymerization initiators suitable for use in the emulsion polymerization process are e.g. persulfates such as ammonium and potassium persulfate, azonitrile compounds such as 4,4′-azo-bis(4-cyanovaleric acid) and likewise peroxide compounds e.g. benzoylperoxide.
- persulfates such as ammonium and potassium persulfate
- azonitrile compounds such as 4,4′-azo-bis(4-cyanovaleric acid)
- peroxide compounds e.g. benzoylperoxide.
- the aqueous dispersion of the present polymer particles i.e. the latex for use in the method according to the present invention may contain conventional emulsifiers.
- Emulsion polymerization methods of a solid water-insoluble monomer coupler in water are described in U.S.Pat. No. 4,080,2ll and Belgian Pat. No. 669,97l.
- a first polymerization method comprises dissolving a solid water-insoluble monomer coupler in an ethylenically unsaturated copolymerizable monomer and an organic solvent which may be completely water-miscible or poorly water-miscible, then adding the resulting solution to an aqueous reaction medium containing an emulsifier and initiating polymerization.
- the organic solvent suited for use in this method must satisfy the following requirements : (l) it is substantially inert to the solid water-insoluble monomer coupler, (2) it does not interrupt the normal action of the free-radical addition polymerization, and (3) it has a low boiling point which makes it possible to easily remove it from the aqueous reaction medium by distillation during and/or after the polymerization.
- the poorly water-miscible solvent has preferably a boiling point of at most l30°C and a sufficiently high vapour pressure so that it can still be removed readily from the aqueous dispersion by applying a vacuum of 665 to l5 mbar at a temperature of 25° to 80°C.
- suitable solvents are methylene chloride, ethyl formate, n-butyl formate, ethyl acetate, n-propyl acetate, isopropyl acetate, butyl acetate, methyl propionate, ethyl propionate, diethyl carbonate, carbon tetrachloride, sym.
- a second polymerization method comprises dissolving a solid water-insoluble monomer coupler in an ethylenically unsaturated copolymerizable monomer, then adding the resulting solution to an aqueous reaction medium containing an emulsifier and a substance initiating polymerization.
- a third polymerization method comprises dispersing a solid water-insoluble monomer coupler and an ethylenically unsaturated copolymerizable monomer or a solid water-insoluble monomer coupler, an ethylenically unsaturated copolymerizable monomer and an organic solvent in an aqueous reaction medium containing an emulsifier and a substance initiating polymerization.
- the hydrophobic monomer is dispersed in the absence of an organic solvent so that no such solvent has to be removed from the eventually obtained latex. It may be advantageous, however, particularly when the dispersion proceeds with difficulty, to dissolve the monomer first in said already mentioned poorly water-miscible organic solvent(s) and to remove the solvent(s) later on.
- the latex polymer of the present invention comprises still other repeating units that are colourless.
- These repeating units are derived e.g. from a monomer or mixture of monomers providing particular physical characteristics to the latex e.g. improved thermal stability, and improved compatibility with hydrophylic binders e.g. gelatin.
- Colourless ethylenically unsaturated monomers that are chemically inert in the sense as defined and that are copolymerisable with the monomers according to general formula (I) are e.g.
- the stability of the latexes used according to the invention may be improved by structural units of an ionogenic comonomer containing at least one long hydrophobic group, e.g. containing at least 8 carbon atoms, and of a strong hydrophilic group, e.g. sulfonic acid, sulfuric acid or phosphonic acid group or salt thereof.
- an ionogenic comonomer containing at least one long hydrophobic group, e.g. containing at least 8 carbon atoms
- a strong hydrophilic group e.g. sulfonic acid, sulfuric acid or phosphonic acid group or salt thereof.
- the particle size of the latexes prepared with the monomers is generally smaller than l00 nm, in most cases smaller than 70 nm.
- the preferred colourable latex particles to be used according to the method of the present invention comprise a polymer selected from the group consisting of a polymer of formula wherein k is from 30 to 60 and y is from 40 to 70 w/w; a polymer of the formula wherein n is from 20 to 70, m is from 30 to 60, and p is from 0 to 40; a polymer of the formula wherein k is from 30 to 60, y is from 20 to 70, and z is from 0 to 40; a polymer of the formula wherein n is from 20 to 70, m is from 0 to 40, and p is from 30 to 60, and a polymer of the formula wherein n is form 40 to 70 and m is from 30 to 60.
- the numbers represented by the symbols k, y, n, m, p and z are precentages by weight.
- Surface-active agents e.g. anionic, cationic and non-ionic surface active agents, which are useful in the dispersing of non-self-dispersing monomers may be used too in the dispersing of the hydrophobic substance to be incorporated and/or adsorbed to the latex particles.
- Such substances are described e.g. in U.S. Patent No. 3,9l2,5l7.
- the labelling of the specific binding agents or preferably of the specific binding proteins with the coloured or colourable latex particles is easily carried out following the methodologies used for the coating of plastics with proteins, including antibodies.
- the coating is easily effected by contacting the particles in an aqueous medium of appropriate pH wherein the desired proteins are dissolved. After a suitable period of time, the excess of protein is removed by repeated centrifugation and washing of the sediment with fresh buffer. After completion of the washing procedure, the latex particles are re-suspended in an aqueous medium which preferably contains an inert protein, e.g. bovine serum albumin, in order to protect the particles from non-selective interactions with non-specific proteins of the test samples.
- an inert protein e.g. bovine serum albumin
- the proteins can also be bound covalently to the latex particles following the procedure described in U.S. Pat. No. 3,857,93l using a water soluble carbodiimide coupling agent.
- the determinations to be made according to the method of this invention may be performed homogeneously or heterogeneously. Homogeneous determinations are particularly simple to perform but require a measurable change of the perceived signal arising from either those latex particles present in the labelled reagent or in the labelled complex formed between the labelled reagent and the particles to be determined. In those instances where no such distinction is possible, heterogeneous determinations will have to be performed.
- Homogeneous determinations are advantageous due to the fact that it is not necessary to physically separate the bound and unbound labelled species, thus reducing the number of steps necessary to perform an assay.
- the reaction between the labelled component and the corresponding binding counterpart causes the measurable change in the label's participation in or modulation of the signal generating moiety necessary to perform a homogeneous determination.
- the distribution of the latex particles between the bound and unbound species may be differentiated by the inability or altered ability of the said latex particles to affect the signal arising therefrom when present in the bound species.
- a homogenous determination may conveniently be performed according to art-known procedures such as, for example, the competitive binding technique.
- the sample containing the analyte is combined with a binding counterpart of the analyte, a labelled reagent comprising a latex particle coupled to the analyte or a specific binding analogue thereof, and if necessary, the other components necessary to convert the precursor of the signal generating moieties in the latex particle to the signal generating moiety itself.
- a sequential determination may be performed whereby the sample and the analyte binding counterpart are first combined and thereafter the detectant reagent added.
- the determination of antibiotics or other binding proteins, receptors, antibodies having specificity for a particular antigen or hapten or binding materials in general can also be performed following a direct technique.
- the liquid medium containing the component to be detected is combined with a labelled reagent comprising a latex particle coupled to a binding counterpart of the analyte and, if necessary, the other components to convert the precursor of the signal generating moieties in the latex particle to the signal generating moieties themselves, whereafter the signal arising from the latex particles which is altered due to the binding, is measured.
- a heterogeneous determination system comprises three basic constituents which are combined simultaneously or subsequently, i.e. the analyte to be detected, a binding counterpart of the analyte and the labelled reagent, where necessary along with other components necessary to convert the precursor of the signal generating moiety in the label to the signal generating moiety itself. If necessary after an appropriate incubation period or periods the labelled reagent becomes bound to the particles to be detected whereby the ratio of the bound species to the unbound species is a function of the amount of analyte being present. The bound and unbound species are physically separated and the amount of label being present in one thereof is determined.
- the said separation may involve conventional techniques such as, for example, by employing a solid-phase antibody or antigen, a second antibody, or a solid-phase second antibody; or by the use of immuno complex precipitation agents, adsorbents, etc.
- the said binding reactions may for example include the so-called competitive binding technique, the sequential saturation technique, the "sandwich technique", etc.
- the preferred determinations to be made according to the method of this invention are heterogeneous determinations which are generally based on the principle that the labelled complex formed between the specific binding protein and the bindable substances is at some time immobilized in such manner that any un-reacted particles can be washed off, whereupon the immobilized particles are detected in situ or, if desired, after disengagement in any other phase derived therefrom.
- the bindable substance to be detected which may be contained in a crude test specimen or in a purified or partly purified fraction derived therefrom, is immobilized on an appropriate immobilizing support prior to its complexing with the labelled binding protein, specific to said bindable substance.
- the immobilization of the bindable substance may be carried out following the usual techniques, e.g. by spotting an aliquot of the test specimen on the immobilizing support or by immersing the latter in the test sample and subsequently drying and optionally washing off non-immobilized material. This is the so-called direct technique.
- immobilizing supports for this technique use can be made of various materials, in general polymeric materials like, nitrocellulose, diazobenzyloxymethyl (DBH)- and diazophenylthioether (DPT) modified cellulose paper, paper, paper or cellulose acetate activated with cyanogen bromide, agarose, nylon, plastics, etc. which may take any form which is convenient for the determination process, e.g. sheets, beats, welled plates, dip-sticks, etc.
- DDH diazobenzyloxymethyl
- DPT diazophenylthioether
- the support is then brought into contact with a suspension of the coloured or colourable latex particles coated with the specific binding protein under conditions which allow complex formation between the binding protein and the corresponding bindable substances.
- a surface active agent like, for example, a polyoxyethylene fatty acid ester (e.g. Tween®). Consequently, at the sites where the bindable substance is immobilized, coated latex particles will be immobilized in turn in amounts proportional to the concentration of the immobilized bindable substance.
- the immobilized bindable substance is first allowed to react with a first binding protein which is specific therefor and subsequently the thus immobilized fase is brought into contact with the coloured or colourable particles coated with a second binding protein which is specific for said first binding protein.
- the direct method is usually employed with relatively pure or purified test samples or fractions.
- the direct method will often be less suitable, as the non-specific immobilization of a large excess of non-desired material will interfere with the sensitivity and specificity of the determination.
- sandwich technique In order to avoid this problem, which is particularly important with regard to routine analyses, use is very often made of an indirect or so-called sandwich technique.
- a purified or enriched primary specific binding protein is immobilized on a solid support.
- the latter is contacted with the test sample under conditions which allow the complexing of the corresponding bindable substances, which consequently become immobilized themselves.
- the latter After removal of the test sample and washing of the support, the latter is contacted with a suspension of coloured or colourable latex particles coated with secondary specific binding proteins which are able to bind to uncomplexed sites of the immobilized bindable substance.
- the detection of the coloured or colourable latex particles is both convenient and simple. When the particles are already coloured their presence can be observed visually, optionally using a microscope or optionally using a colorimeter or spectrophotometer. Colorimetric or spectrophotometric determinations will be preferred when quantitative determinations are desired.
- the coloured signal can be observed at the binding side itself or, after disengagement, in the resulting suspension or any fraction or phase derived therefrom.
- colourable particles When colourable particles are used instead, it will be necessary to convert them prior to the evaluation into the corresponding coloured particles by allowing them to react with the particular reagents known to be effective for effecting such conversion.
- colour couplers of the type described hereinabove it will be appropriate to contact the particles first with a strong oxidant, such as a peroxide, perborate, peroxoic acid or preferably persulfate and thereafter with a photographic developer, e.g. a phenylene diamine.
- the specific binding proteins which can be employed in the method according to the invention can be of various natures but will in many instances be antibodies to specified antigens or haptens.
- specific binding substances other than antibodies there can be mentioned lectins, which specifically bind glycoproteins and Staphylococcus protein A which specifically binds immunoglobulins of various animal species.
- Antibodies may be polyclonal or monoclonal, the latter having the advantage of being more specific.
- the binding reaction will in almost all cases be allowed to proceed under mild conditions.
- the reaction mixture will in general be an aqueous medium with any desirable organic cosolvents being present in minor amounts.
- the temperature of the reaction will be maintained at a constant level in normal circumstances throughout the incubation period and the enzyme measurement step. Temperatures will generally be between 5 and 50°C, more usually between 20 and 40°C. Preferably the reaction will proceed at room temperature.
- the pH of the reaction mixture will vary between 5 and l0, more usually between 6 and 9.
- the concentration of various reagents will depend on the level of analyte expected in the test medium, with such level usually being between l0 ⁇ 3 and l0 ⁇ 12M.
- the method according to the invention has an extremely wide field of application. In principle it can be applied to the detection and/or quantitative determination of any substances for which specific binding proteins exist.
- substances comprise but are not limited to cell surface and tissue antigens, biological substances excreted by or derived from living organisms, particularly biological substances occurring in biological fluids such as saliva, lymph, blood and its derived fractions such as, plasma and serum, urine, cerebrospinal fluid, amnion fluid, etc.
- Substances which can be detected include, proteins, polypeptides, peptides, like enzymes, hormones, structural proteins; nucleic acids; vitamins; polysaccharides; toxins; alkaloids; glycoproteins; haptens; metabolites; pharmacological agents; steroids, and any other molecules for which a specific binding counterpart exists in biological systems or can be synthesized.
- Representative protein analytes include the classes of protamines, mucoproteins, glycoproteins, globulins, albumins, scleroproteins, phosphoproteins, histones, lipoproteins, chromoproteins, and nucleoproteins.
- proteins examples include prealbumin, ⁇ 1-lipoprotein, human serum albumin, ⁇ 1-acid glycoprotein, ⁇ 1-antitrypsin, ⁇ 1-glycoprotein, transcortin, thyroxine binding globulin, haptoglobin, hemoglobin, myoglobin, ceruloplasmin, ⁇ 2-lipoprotein, ⁇ 2-macroglobulin, ⁇ -lipoprotein, erythroprotein, transferin, hemopexin, fibrinogen, the immunoglobulins such as IgG, IgM, IgA, IgD, and IgE, and their fragments, e.g., F c and F ab , complement factors, prolactin, blood clotting factors such as fibrinogen, thrombin and so forth, insulin, melanotropin, somatotropin, thyrotropin, follicle stimulating hormone, luteinizing hormone, gonadotropin, thryroid stimulating hormone, placental lactogen
- hapten analytes include the general classes of drugs, metabolites, hormones, vitamins, and the like organic compounds.
- Haptenic hormones include thyroxine and triidothyronine.
- Vitamins include vitamins A, B, e.g., B12, C, D, E and K, folic acid and thiamine, Drugs include antibiotics such as aminoglycosides, e.g., gentamicin, tobramycin, amidacin, sisomicin, kanamycin, and netilmicin, penicillin, tetracycline, terramycin, chloromycetin, and actinomycetin; nucleosides and nucleotides such as adenosine diphosphate (ADP) adenosine triphosphate (ATP), flavin mononucleotide (FMN), nicotinamide adenine dinucleotide (NAD) and its phosphate derivative (NADP), thymidine,
- cardiac glycosides and derivatives of benzodiazepine, benzimidazole, piperidine, piperazine, imidazole, triazole, pyridazine, l,2,4-triazinedione or 2,3,5,6-tetrahydro-imidazo[2,l-b]thiazoles, or amides, hydratropic acid derivatives or trialkylamines.
- Benzimidazole derivatives comprise thiabendazole, fuberidazole, ciclobendazole, oxibendazole, parbendazole, cambendazole, mebendazole, fenbendazole, flubendazole, albendazole, oxfendazole, nocodazole and astemizole.
- Piperidine derivatives comprise diphenoxylate, phenoperidine, haloperidol, haloperidol decanoate, bromperidol decanoate, bromperidol, moperone, trifluperidol, pipamperone, piritramide, fentanyl, benperidol, droperidol, benzitramide, benzetimide, domperidone, sufentanil, carfentanil, alfentanil, dexetimide, milenperone, difenoxin, fluspirilene, penfluridol, pimozide, lorcainide, loperamide, astemizole, ketanserine, levocabastine, cisapride, altanserin, ritanserin, 3-[2-[4-(4-fluorobenzoyl)-l-piperidinyl]ethyl]-2,7-dimethyl-4 H -pyr
- Piperazine derivatives include azaperone, fluanisone, lidoflazine, flunarizine, mianserine, oxatomide, mioflazine, clocinizine and cinnarizine.
- imidazole derivatives are metronidazole, ornidazole, ipronidazole, tinidazole, isoconazole, nimorazole, miconazole, burimamide, metiamide, metomidate, enilconazole, or imazalil, etomidate, econazole, clotrimazole, carnidazole, cimetidine, doconazole, sulconazole, parconazole, orconazole, butoconazole, triadiminole, tioconazole, valconazole, fluotrimazole, ketoconazole, oxiconazole, lombazole, bifonazole, oxmetidine, fenticonazole, tubulazole and (Z)-l-[2-chloro-2-(2,4-dichlorophenyl)ethenyl]-l H -imidazole.
- Triazole derivatives comprise virazole, azaconazole, etaconazole, propiconazole, penconazole, itraconazole and terconazole.
- Pyridazine derivative comprise for example, 3-chloro-6-[3,6-dihydro-4-(3-methylphenyl)-l(2 H )-pyridinyl]pyridazine, 3-methoxy-6-[4-(3-methylphenyl)-l-piperazinyl]pyridazine and the compounds of Publ. Eur. Pat. Appl. No. 0,l56,433.
- l,2,4-Triazinediones comprise for example, 2-chloro- ⁇ -(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-l,2,4-triazin-2(3 H )-yl)benzeneacetonitrile, 2,6-dichloro- ⁇ -(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-l,2,4-triazin-2(3 H )-yl)benzeneacetonitrile and the compounds of Publ. Eur. Pat. Appl. No. 0,l70,3l6.
- Trialkylamines are, for example, diisopromine, prozapine.
- 2,3,5,6-Tetrahydro-imidazo[2,l-b]thiazoles comprise, for example, tetramisole or levamisole.
- Amides comprise for example, closantel, ambucetamide, isopropamide, buzepide metiodide, dextromoramide.
- a hydratropic acid derivative is, for example, suprofen.
- the purposes of the determinations can be multiple. In certain applications they will be used merely as a scientific tool, to visualize particular substances, e.g. on histological coupes, on chromatograms, electrophoretograms, blots, etc. For example, when applying different lables to different specific proteins or other bindable substances on a chromatogram, electrophoretogram, protein blot etc., a reference pattern is obtained which can advantageously be used to localize other proteins or other substances.
- the method of the invention will find utility in a wide variety of diagnostic tests such as, for example, the following: the detection and characterisation of subpopulations of T-lymphocytes; pregnancy tests based on the presence of certain hormones (choriotrophic gonadotropin) in the urine, diagnostic tests for various infections diseases of i.a. fungal, bacterial and in particular viral origin, such as, for example, hepatitis B, auto-immune-diseases (AIDS), gonorrhoea, rubella, poliomyelitis, etc.
- diagnostic tests such as, for example, the following: the detection and characterisation of subpopulations of T-lymphocytes; pregnancy tests based on the presence of certain hormones (choriotrophic gonadotropin) in the urine, diagnostic tests for various infections diseases of i.a. fungal, bacterial and in particular viral origin, such as, for example, hepatitis B, auto-immune-diseases (AIDS), gonorrhoea,
- Diagnostics for metabolic, endocrinological and various endogenous diseases including diagnostics for the detection of congenital malfunctions of embryo's based on the presence of specific proteins in the amnion fluid.
- multivalent diagnostics can be prepared which allow the simultaneous detection and/or determination of more than one bindable substance.
- the method lends itself particularly for routine tests, not only for use by specialists and technicians in the laboratory, but also for use by laymen who have no skills in the relevent technical field.
- the method can also be easily automated which is an important factor when large numbers of identical determinations must be carried out, e.g. in blood banks and specialized clinical laboratories.
- the invention further comprises reagent systems which comprise all of the essential chemical elements required to conduct a desired assay method encompassed by the present invention.
- the reagent system is presented in a commercially packaged form, as a composition or admixture where the compatability of the reagents will allow, in a test device configuration, or as a test kit, i.e., a packaged combination of one or more containers holding the necessary reagents. Included in the reagent system are the reagents appropriate for the binding reaction system desired, always requiring a labelled reagent and the other components necessary to produce the signal-generating reaction.
- binding reaction reagents can include, in addition to the labelled reagent, a binding counterpart to the analyte, and so forth.
- the reagent system can include other reagents as are known in the art and which may be desirable from a commercial and user standpoint, such as buffers, diluents, standards, and so forth.
- the invention comprises test kits for the qualitative or quantitative determination of specific bindable substances which comprise, besides other reagents, an aqueous suspension of latex particles which are coated with specific binding proteins to said bindable substances or to primary specific binding proteins to said bindable substances.
- the suspensions of the colour coupler latexes M1, C2 and Y1 used in these examples have the following compositions:
- a suspension of colour coupler latex M1, C2 and Y1 was diluted to a 2% (polymer content) suspension using a sodium carbonate dilution buffer (0.0l5 M Na2CO3, 0.035 M NaHCO3, 0.2 g/l NaN3, pH 9.3).
- a protein (antibody) solution, containing 0.5 mg/ml affinity-purified goat anti-mouse immunoglobulin was added to 5 ml of the latex suspension.
- Latex-antibody complexes were reacted with antigen which was fixed to a nitrocellulose membrane.
- a dilution series of the antigen was made in a buffer consisting of 0.02 M Tris(hydroxymethyl)aminoethane - 0.l5 M NaCl - 0.5 g/l NaN3, (pH 8.2, with HCl) with 50 ⁇ g/ml albumin as carrier.
- a concentration series of 250 - l25 - 62.5 - 3l - l5.5 - 7.75 - 3.9 - l.9 - 0.8 and 0.4 ng/ ⁇ l was prepared and l ⁇ l thereof was spotted onto nitrocellulose strips (0.6 ⁇ 6cm).
- nitrocellulose strips were treated with 0.05 M sodium phosphate (pH 7.5) - 5% (v/v) Tween® solution for 30 minutes at 37°C, and subsequently washed three times with water for l0 min.
- 0.05 M sodium phosphate (pH 7.5) - 5% (v/v) Tween® solution for 30 minutes at 37°C, and subsequently washed three times with water for l0 min.
- albumin instead of immunoglobulin (antigen) were in the same way spotted.
- the nitrocellulose strips were incubated for 2-3 hours with the latex suspension, prepared as mentioned above.
- the optimal concentration of protein (antibodies) to be coupled to the latex was determined in the following test procedure. A series of solutions of various concentration, (antibody concentrations of 2 - l - 0.5 - 0.l mg/ml) was added to 5 ml of the 2% latex suspension. The thus obtained mixtures were further treated following the same described hereinabove. The colour intensities obtained with the latex-antibody complexes prepared with the various concentrations of antibody were compared. It appeared that the optimal concentration of antibodies was 0.5 mg/ml since higher concentrations gave no increase of colour intensity of the spots, lower concentrations gave less intensity.
- the detection sensitivity is defined as the minimal detectable spot in the antigen dilution series. This sensitivity varies with the type of latex. In a typical experiment the following sensitivities were found: colour coupler latex M1 l.9 ng/ ⁇ l; colour coupler latex Y1 l5.5 ng/ ⁇ l; colour coupler latex C2 7.7 ng/ ⁇ l.
- a suspension of colour coupler latex C1 was diluted to 2% (polymer content) in a sodium carbonate dilution buffer (0.0l5 M Na2CO3, 0.035 M NaHCO3, 0.2 g/l NaN3, pH 9.3).
- l25 mg normal human immunoglobulin dissolved in 5ml of the aforementioned carbonate buffer were mixed with 250 ml of the diluted latex suspension. This mixture was stirred overnight at room temperature to allow the immunoglobulin to adsorb on the latex beads.
- l00 ml of a 5% (w.v) bovine serum albumin (BSA) solution in a 50 mM phosphate buffer at pH 7.5 were added to the stirred mixture which was then put at 37°C for 30 min.
- the remaining unbound immunoglobulin and BSA were washed away from the latex particles with phosphate-BSA-Tween®-NaCl buffer (0.05 M sodium phosphate, 5 g/l BSA, 5 ml/l Tween 20®, l M NaCl, 0.5 g/l NaN3, pH 7.5).
- the latex suspension was then brought at the original volume of 250 ml in the same phosphate-BSA-Tween®-NaCl buffer.
- a suspension of colour coupler latex M1 was diluted to 2% (polymer content) in the carbonate buffer described hereinabove. 2 ml of anti-C-reactive protein (anti-CRP) antibodies (39.6 mg/ml), were mixed with 250 ml of the diluted latex suspension. This mixture was stirred overnight at room temperature.
- anti-CRP anti-C-reactive protein
- the latex particles were washed in glycin-Triton-SDS® buffer (0.l M glycin, 0.l M NaCl, 0.l2 mg/ml NaOH, l g/l NaN3, l ml/l Triton X705® 50%, l4 mg/l sodium dodecyl sulphate (SDS). Afterwards, the suspension was diluted ten times in a 50 mM phosphate buffer (pH 7.5) containing 5% (w/v) BSA, and kept at 37°C for 30 min. The latex particles were then washed in the phosphate-BSA-Tween®-NaCl buffer described hereinabove. During this process, the volume of the latex suspension was reduced to the original 250 ml.
- glycin-Triton-SDS® buffer 0.l M glycin, 0.l M NaCl, 0.l2 mg/ml NaOH, l g/l NaN3,
- Sticks (5 ⁇ l00 mm) were made out of 0.2 mm polyester sheets. One 5 ⁇ 5 mm human immunoglobulin-containing piece of filter paper and one 5 ⁇ 5 mm anti-CRP antibody-containing piece of filter paper were glued next to each other, close to one edge of the stick. Care was taken to leave a l mm gap between both pieces of paper. The glue was allowed to dry at room temperature overnight. The assembled dip-sticks were stored at 4°C.
- 0.5 to l ml of a patient's serum was put in a l0 ml polystyrene test tube.
- the dip-stick was added for 30 to 60 min in a way that both activated sites were properly immersed.
- the dip-stick was then washed with running tap water for about l0 s.
- the stick was put in a mixture of l ml anti-CRP colour coupled latex and l ml anti-rheumatoid factor colour coupled latex for 30 to 60 min.
- the dipstick was washed again with tap water and held for a few seconds in a l0% persulfate solution.
- the colour was developed by immersing the stick for about five seconds in a developer containing 4-(butyl, N - ⁇ -sulfobutyl)amino-aniline as developing agent.
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Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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AT86202231T ATE87743T1 (de) | 1985-12-23 | 1986-12-10 | Verfahren zum nachweis von spezifischen bindemitteln und ihren korrespondierenden bindbaren stoffen. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US81258685A | 1985-12-23 | 1985-12-23 | |
US812586 | 1985-12-23 |
Publications (3)
Publication Number | Publication Date |
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EP0227173A2 true EP0227173A2 (fr) | 1987-07-01 |
EP0227173A3 EP0227173A3 (en) | 1989-08-02 |
EP0227173B1 EP0227173B1 (fr) | 1993-03-31 |
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Application Number | Title | Priority Date | Filing Date |
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EP86202231A Expired - Lifetime EP0227173B1 (fr) | 1985-12-23 | 1986-12-10 | Procédé pour la détection des agents liants spécifiques et leurs substances liables correspondantes |
Country Status (7)
Country | Link |
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US (2) | US4837168A (fr) |
EP (1) | EP0227173B1 (fr) |
JP (1) | JP2509201B2 (fr) |
AT (1) | ATE87743T1 (fr) |
CA (1) | CA1291031C (fr) |
DE (1) | DE3688184T2 (fr) |
ES (1) | ES2054617T3 (fr) |
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US5266497A (en) * | 1990-08-31 | 1993-11-30 | Japan Synthetic Rubber Co., Ltd. | Immunochromatographic assay with improved colored latex |
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Families Citing this family (232)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5622871A (en) | 1987-04-27 | 1997-04-22 | Unilever Patent Holdings B.V. | Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents |
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JPH0737990B2 (ja) * | 1990-10-12 | 1995-04-26 | 寳酒造株式会社 | 糖類の標識方法及び糖類標識用キット |
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US5877028A (en) | 1991-05-29 | 1999-03-02 | Smithkline Diagnostics, Inc. | Immunochromatographic assay device |
US6168956B1 (en) | 1991-05-29 | 2001-01-02 | Beckman Coulter, Inc. | Multiple component chromatographic assay device |
US5998220A (en) | 1991-05-29 | 1999-12-07 | Beckman Coulter, Inc. | Opposable-element assay devices, kits, and methods employing them |
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US5354692A (en) * | 1992-09-08 | 1994-10-11 | Pacific Biotech, Inc. | Analyte detection device including a hydrophobic barrier for improved fluid flow |
US5352585A (en) * | 1993-06-29 | 1994-10-04 | Bio-Rad Laboratories, Inc. | System for benzodiazepine detection |
GB2314333B (en) * | 1993-10-05 | 1998-04-29 | Asahi Optical Co Ltd | Antigen or antibody immobilised on dyed composite comprising polymer granules coated with a calcium phosphate |
CH686518A5 (de) * | 1993-10-05 | 1996-04-15 | Asahi Optical Co Ltd | Granulares Polymerkomposit, Herstellungsverfahren fur dieses und diagnostische Mittel. |
CA2167362A1 (fr) * | 1995-02-10 | 1996-08-11 | Alexei Dmitri Klimov | Appareil et methode pour la realisation d'un essai de liaisonnement entre deux materiaux absorbants |
EP2258726A1 (fr) | 1995-06-14 | 2010-12-08 | The Regents of the University of California | Anticorps humains à haute affinité pour c-erbB-2 |
US7455964B1 (en) | 1996-07-15 | 2008-11-25 | The Hospital For Sick Children | Genes from the 20q13 amplicon and their uses |
IL126544A (en) | 1996-04-25 | 2004-08-31 | Genicon Sciences Inc | Test for component detection using detectable particles in diffused light |
US6586193B2 (en) * | 1996-04-25 | 2003-07-01 | Genicon Sciences Corporation | Analyte assay using particulate labels |
DE19621312A1 (de) * | 1996-05-28 | 1997-12-04 | Bayer Ag | Maskierung der Hintergrundfluoreszenz und Signalverstärkung bei der optischen Analyse biologisch medizinischer Assays |
ATE245194T1 (de) | 1996-10-01 | 2003-08-15 | Geron Corp | Katalytische untereinheit der menschlichen telomerase |
US5879951A (en) | 1997-01-29 | 1999-03-09 | Smithkline Diagnostics, Inc. | Opposable-element assay device employing unidirectional flow |
EP2172478A3 (fr) | 1997-02-07 | 2010-07-28 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Facteur III neurotrophe dépendant de l'activité (ADNF III) |
US5981296A (en) * | 1997-02-18 | 1999-11-09 | Dade Behring Inc. | Stabilization of particle reagents |
US6103536A (en) | 1997-05-02 | 2000-08-15 | Silver Lake Research Corporation | Internally referenced competitive assays |
US5939252A (en) | 1997-05-09 | 1999-08-17 | Lennon; Donald J. | Detachable-element assay device |
US6960457B1 (en) | 1997-09-04 | 2005-11-01 | Stanford University | Reversible immobilization of arginine-tagged moieties on a silicate surface |
US6194222B1 (en) * | 1998-01-05 | 2001-02-27 | Biosite Diagnostics, Inc. | Methods for monitoring the status of assays and immunoassays |
US7713703B1 (en) | 2000-11-13 | 2010-05-11 | Biosite, Inc. | Methods for monitoring the status of assays and immunoassays |
US6265163B1 (en) | 1998-01-09 | 2001-07-24 | Lynx Therapeutics, Inc. | Solid phase selection of differentially expressed genes |
US6764830B1 (en) | 1998-01-23 | 2004-07-20 | The Regents Of The University Of California | Thermomyces lanuginosus kinesin motor protein and methods of screening for modulators of kinesin proteins |
US7402400B2 (en) | 2001-07-03 | 2008-07-22 | Regents Of The University Of California | Mammalian sweet taste receptors |
ATE273516T1 (de) * | 1999-06-23 | 2004-08-15 | Cornell Res Foundation Inc | Entwässerung/rehydratisierung von markierten liposomen auf einer prüfeinrichtung |
US6703248B1 (en) * | 1999-12-15 | 2004-03-09 | Dade Behring Marburg Gmbh | Particles for diagnostic and therapeutic use |
TW201006846A (en) | 2000-03-07 | 2010-02-16 | Senomyx Inc | T1R taste receptor and genes encidung same |
EP1287364B1 (fr) | 2000-04-29 | 2008-10-22 | University Of Iowa Research Foundation | Diagnostic et therapeutique pour des troubles lies a une degenerescence maculaire |
DE10042023C2 (de) * | 2000-08-08 | 2003-04-10 | Biognostic Ag | Kapseln, die feste Teilchen signalerzeugender Substanzen einkapseln, und deren Verwendung bei Bioassays zum Nachweis von Zielmolekülen in einer Probe |
GB0021303D0 (en) * | 2000-08-30 | 2000-10-18 | Medinnova Sf | Use |
AU2001294654A1 (en) * | 2000-09-25 | 2002-04-08 | The Regents Of The University Of California | Model for neurodegenerative diseases involving amyloid accumulation |
TW201022287A (en) | 2001-01-03 | 2010-06-16 | Senomyx Inc | T1R taste receptors and genes encoding same |
US7691645B2 (en) * | 2001-01-09 | 2010-04-06 | Agilent Technologies, Inc. | Immunosubtraction method |
US7361472B2 (en) * | 2001-02-23 | 2008-04-22 | Invitrogen Corporation | Methods for providing extended dynamic range in analyte assays |
AU2002326315B2 (en) | 2001-06-26 | 2007-07-05 | Senomyx, Inc. | T1R hetero-oligomeric taste receptors and cell lines that express said receptors and use thereof for identification of taste compounds |
JP4265149B2 (ja) * | 2001-07-25 | 2009-05-20 | セイコーエプソン株式会社 | 電気光学装置、電気光学装置の製造方法 |
US7300633B2 (en) | 2001-07-25 | 2007-11-27 | Oakville Hong Kong Company Limited | Specimen collection container |
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MXPA04002817A (es) | 2001-09-27 | 2004-07-05 | Pioneer Hi Bred Int | Polinucleotidos de fitato y metodos de uso. |
US20030099621A1 (en) | 2001-11-29 | 2003-05-29 | Robert Chow | Stem cell screening and transplantation therapy for HIV infection |
US6837171B1 (en) | 2002-04-29 | 2005-01-04 | Palmer/Snyder Furniture Company | Lightweight table with unitized table top |
US8367013B2 (en) | 2001-12-24 | 2013-02-05 | Kimberly-Clark Worldwide, Inc. | Reading device, method, and system for conducting lateral flow assays |
US20030119203A1 (en) | 2001-12-24 | 2003-06-26 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay devices and methods for conducting assays |
AU2003211157A1 (en) * | 2002-02-21 | 2003-09-09 | Eastern Virginia Medical School | Protein biomarkers that distinguish prostate cancer from non-malignant cells |
US20030162178A1 (en) * | 2002-02-25 | 2003-08-28 | O'hagan David | Variable microarray and methods of detecting one or more anlaytes in a sample |
ATE478337T1 (de) * | 2002-05-31 | 2010-09-15 | Cornell Res Foundation Inc | Methoden zum nachweis analyten in proben |
WO2005016232A2 (fr) | 2002-08-01 | 2005-02-24 | The Regents Of The University Of California | Anticorps monoclonaux therapeutiques qui neutralisent les neurotoxines botuliques |
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US7432105B2 (en) | 2002-08-27 | 2008-10-07 | Kimberly-Clark Worldwide, Inc. | Self-calibration system for a magnetic binding assay |
CA2500407C (fr) * | 2002-10-11 | 2009-05-26 | Zbx Corporation | Dispositifs de diagnostic |
US7781172B2 (en) | 2003-11-21 | 2010-08-24 | Kimberly-Clark Worldwide, Inc. | Method for extending the dynamic detection range of assay devices |
US20040106190A1 (en) * | 2002-12-03 | 2004-06-03 | Kimberly-Clark Worldwide, Inc. | Flow-through assay devices |
US7247500B2 (en) | 2002-12-19 | 2007-07-24 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in membrane-based assay devices |
US20040121334A1 (en) * | 2002-12-19 | 2004-06-24 | Kimberly-Clark Worldwide, Inc. | Self-calibrated flow-through assay devices |
WO2004058938A2 (fr) * | 2002-12-31 | 2004-07-15 | Pharmacia & Upjohn Company Llc | Sequences de l-pbe canine |
WO2004057940A2 (fr) * | 2002-12-31 | 2004-07-15 | Pharmacia & Upjohn Company Llc | Sequences de recepteurs d'hydrocarbure dioxine/aryle (ahr) canins |
JP2006512075A (ja) * | 2002-12-31 | 2006-04-13 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | イヌcyp1a2配列 |
US7560272B2 (en) | 2003-01-04 | 2009-07-14 | Inverness Medical Switzerland Gmbh | Specimen collection and assay container |
US6977079B2 (en) * | 2003-01-17 | 2005-12-20 | Regents Of The University Of Minnesota | Avian pneumovirus vaccine |
US7157551B2 (en) * | 2003-02-14 | 2007-01-02 | Cephalon, Inc. | Compositions and methods for the detection and treatment of methylthioadenosine phosphorylase deficient cancers |
US20040197819A1 (en) | 2003-04-03 | 2004-10-07 | Kimberly-Clark Worldwide, Inc. | Assay devices that utilize hollow particles |
US7851209B2 (en) * | 2003-04-03 | 2010-12-14 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in assay devices |
US7321065B2 (en) * | 2003-04-18 | 2008-01-22 | The Regents Of The University Of California | Thyronamine derivatives and analogs and methods of use thereof |
CA2528005A1 (fr) * | 2003-06-12 | 2004-12-23 | Vaxgen, Inc. | Glycoproteines d'enveloppe du vih-1 a structure disulfure inhabituelle |
US20050014734A1 (en) * | 2003-07-18 | 2005-01-20 | Genovate Biotechnology Co., Ltd. | Modulation of interleukin-10 by DHEA |
US20050019214A1 (en) * | 2003-07-23 | 2005-01-27 | Eastman Kodak Company | Colorable polymeric particles with biological probes |
US6914106B2 (en) * | 2003-07-23 | 2005-07-05 | Eastman Kodak Company | Polymer microspheres containing latent colorants and method of preparation |
BRPI0413347A (pt) | 2003-08-06 | 2006-10-10 | Senomyx Inc | novos sabores, modificadores de sabor, agentes de sabor, realçadores de sabor, agentes de sabor e/ou realçadores umami ou doces, e utilização correspondente |
US7517495B2 (en) | 2003-08-25 | 2009-04-14 | Inverness Medical Switzerland Gmbh | Biological specimen collection and analysis system |
US20050079484A1 (en) * | 2003-10-10 | 2005-04-14 | Heineman William Richard | Method of detecting biological materials in liquid |
AU2004286235B2 (en) | 2003-10-21 | 2011-05-12 | Orion Genomics Llc | Differential enzymatic fragmentation |
US7943395B2 (en) | 2003-11-21 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Extension of the dynamic detection range of assay devices |
US20050112703A1 (en) | 2003-11-21 | 2005-05-26 | Kimberly-Clark Worldwide, Inc. | Membrane-based lateral flow assay devices that utilize phosphorescent detection |
US7713748B2 (en) | 2003-11-21 | 2010-05-11 | Kimberly-Clark Worldwide, Inc. | Method of reducing the sensitivity of assay devices |
EP1689783B1 (fr) | 2003-11-25 | 2010-05-19 | The Government Of The United States, As Represented by The Secretary Of Health And Human Services | Anticorps anti-cd22 et immunoconjugues mutes |
US7943089B2 (en) | 2003-12-19 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Laminated assay devices |
US20050141843A1 (en) * | 2003-12-31 | 2005-06-30 | Invitrogen Corporation | Waveguide comprising scattered light detectable particles |
EP1713900A4 (fr) * | 2004-01-27 | 2009-06-17 | Compugen Ltd | Procedes et systemes pour l'annotation de sequences de biomolecules |
DK2712617T3 (en) | 2004-03-12 | 2017-02-13 | Intercept Pharmaceuticals Inc | Treatment of fibrosis with Fxr ligands. |
JP4659025B2 (ja) | 2004-04-15 | 2011-03-30 | ユニバーシティ オブ フロリダ リサーチ ファンデーション インコーポレーティッド | 神経系傷害および他の神経障害についての生物マーカーとしての神経タンパク質 |
CA2564769C (fr) | 2004-04-23 | 2013-12-17 | Pharmacia & Upjohn Company Llc | Facteur de permissivite cellulaire pour virus, et son utilisation |
US7939251B2 (en) | 2004-05-06 | 2011-05-10 | Roche Molecular Systems, Inc. | SENP1 as a marker for cancer |
AR049924A1 (es) * | 2004-06-18 | 2006-09-13 | Univ Minnesota | Identificacion de organismos viralmente infectados y vacunados |
US20080268426A1 (en) * | 2004-06-18 | 2008-10-30 | Regents Of The University Of Minnesota | Identifying virally infected and vaccinated organisms |
CA2571243A1 (fr) | 2004-06-21 | 2006-01-05 | The Board Of Trustees Of The Leland Stanford Junior University | Genes et voies exprimes de maniere differentielle dans des troubles bipolaires et/ou troubles depressifs majeurs |
US7521226B2 (en) | 2004-06-30 | 2009-04-21 | Kimberly-Clark Worldwide, Inc. | One-step enzymatic and amine detection technique |
US7510858B2 (en) * | 2004-08-02 | 2009-03-31 | Janssen Pharmaceutica N.V. | IRAK 1c splice variant and its use |
US7598080B2 (en) * | 2004-08-20 | 2009-10-06 | Carl Deirmengian | Diagnostic assay for source of inflammation |
US7893197B2 (en) * | 2004-08-25 | 2011-02-22 | Janssen Pharmaceutica N.V. | Relaxin-3 chimeric polypeptides and their preparation and use |
WO2006047417A2 (fr) | 2004-10-21 | 2006-05-04 | University Of Florida Research Foundation, Inc. | Detection de biomarqueurs du recepteur cannabinoide et utilisations |
EP1814573B1 (fr) | 2004-10-29 | 2016-03-09 | ratiopharm GmbH | Remodelage et glycopegylation du facteur de croissance des fibroblastes (fgf) |
US7700738B2 (en) | 2005-01-27 | 2010-04-20 | The Regents Of The University Of California | Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins |
JP5202296B2 (ja) | 2005-04-01 | 2013-06-05 | ユニバーシティ オブ フロリダ リサーチ ファウンデーション,インコーポレイティド | 肝臓傷害のバイオマーカー |
US8048638B2 (en) * | 2005-04-01 | 2011-11-01 | University Of Florida Research Foundation, Inc. | Biomarkers of liver injury |
CN101351710B (zh) | 2005-04-04 | 2013-06-05 | 生物基因Idecma公司 | 评价对治疗性蛋白质的免疫应答的方法和产品 |
EP1871795A4 (fr) | 2005-04-08 | 2010-03-31 | Biogenerix Ag | Compositions et méthodes utilisées pour la préparation de mutants par glycosylation de l'hormone de croissance humaine résistant à la protéase |
ES2386973T3 (es) | 2005-06-24 | 2012-09-10 | Regents Of The University Of Minnesota | Virus PRRS, clones infecciosos, mutantes de los mismos, y métodos de utilización |
US7642086B2 (en) | 2005-08-09 | 2010-01-05 | Canon Kabushiki Kaisha | Labeled probe bound object, method for producing the same and method for using the same |
KR100956503B1 (ko) | 2005-09-01 | 2010-05-07 | 가부시키가이샤 무라타 세이사쿠쇼 | 피검체의 산란 계수의 측정방법 및 측정장치 |
US8193328B2 (en) * | 2005-09-08 | 2012-06-05 | Philadelphia Health & Education Corporation | Identification of modulators of serine protease inhibitor Kazal and their use as anti-cancer and anti-viral agents |
IL172297A (en) | 2005-10-03 | 2016-03-31 | Compugen Ltd | Soluble vegfr-1 variants for the diagnosis of preeclampsia |
US20090155850A1 (en) * | 2005-10-28 | 2009-06-18 | The Florida International University Board Of Trustees | Horse:Human Chimeric Antibodies |
EP1945261A4 (fr) | 2005-11-07 | 2010-05-12 | Scripps Research Inst | Compositions et procédés destinés à controler la spécificité de la signalisation du facteur tissulaire |
EP2564864B8 (fr) | 2005-11-12 | 2015-05-13 | The Board of Trustees of The Leland Stanford Junior University | Méthodes associées au FGF2 pour diagnostiquer et traiter une dépression |
US9056291B2 (en) | 2005-11-30 | 2015-06-16 | Micronics, Inc. | Microfluidic reactor system |
US7763453B2 (en) | 2005-11-30 | 2010-07-27 | Micronics, Inc. | Microfluidic mixing and analytic apparatus |
EP3153860A3 (fr) | 2005-12-22 | 2017-06-14 | Abbott Molecular Inc. | Procédés et combinaisons de marqueurs pour dépister la prédisposition au cancer du poumon |
US9347945B2 (en) | 2005-12-22 | 2016-05-24 | Abbott Molecular Inc. | Methods and marker combinations for screening for predisposition to lung cancer |
CA2637267A1 (fr) | 2006-01-16 | 2007-07-19 | Compugen Ltd. | Nouvelles sequences de nucleotides et d'acides amines et leurs procedes d'utilisation pour le diagnostic |
CA2641513C (fr) | 2006-02-28 | 2021-09-21 | Elan Pharmaceuticals, Inc. | Methodes pour traiter des maladies inflammatoires et auto-immunes avec du natalizumab |
KR20080104343A (ko) | 2006-03-03 | 2008-12-02 | 엘란 파마슈티칼스, 인크. | 나탈리주마브로 염증 및 자가면역 질환을 치료하는 방법 |
EP3398452A3 (fr) | 2006-04-21 | 2018-11-28 | Senomyx, Inc. | Compositions comestibles comprenant des aromatisants salés très puissants et leurs procédés de production |
EP2041573B1 (fr) * | 2006-06-23 | 2019-09-04 | PerkinElmer Health Sciences, Inc. | Procédés et dispositifs destinés à des dosages immunologiques microfluidiques pratiqués au point de service |
EP2053961A4 (fr) * | 2006-08-09 | 2013-05-01 | Biogen Idec Inc | Procédé de distribution d'un médicament |
US7569396B1 (en) | 2006-09-08 | 2009-08-04 | Purplecow Llc | Caffeine detection using internally referenced competitive assays |
US7919331B2 (en) * | 2006-12-21 | 2011-04-05 | Silver Lake Research Corporation | Chromatographic test strips for one or more analytes |
WO2008118324A2 (fr) | 2007-03-26 | 2008-10-02 | Macrogenics, Inc. | Composition et procédé de traitement du cancer avec un anticorps anti-uroplakine ib |
US7572990B2 (en) * | 2007-03-30 | 2009-08-11 | Intermec Ip Corp. | Keypad overlay membrane |
WO2008153926A2 (fr) | 2007-06-05 | 2008-12-18 | Yale University | Inhibiteurs de récepteurs tyrosine kinases et leurs méthodes d'utilisation |
PL2769729T3 (pl) | 2007-09-04 | 2019-09-30 | Compugen Ltd. | Polipeptydy i polinukleotydy i ich zastosowanie jako cel dla leków do wytwarzania leków i środków biologicznych |
EP2245055A2 (fr) * | 2008-01-31 | 2010-11-03 | Compugen Ltd. | Polypeptides et polynucléotides et leurs utilisations en tant que cible médicamenteuse pour produire des médicaments et des produits biologiques |
US20110136166A1 (en) * | 2008-03-14 | 2011-06-09 | Eastern Virginia Medical School | Imaging Mass Spectrometry for Improved Prostrate Cancer Diagnostics |
US8993231B2 (en) * | 2008-03-18 | 2015-03-31 | Marshall University Research Corporation | Methods for stem cell production and therapy |
PL2247304T3 (pl) | 2008-04-02 | 2017-01-31 | Macrogenics, Inc. | Przeciwciała specyficzne wobec HER2/neu oraz sposoby ich zastosowania |
CN106349390B (zh) | 2008-04-02 | 2019-12-10 | 宏观基因有限公司 | Bcr-复合体-特异性抗体和其使用方法 |
WO2010033279A2 (fr) | 2008-06-04 | 2010-03-25 | Macrogenics, Inc. | <sb>anticorps à liaison alteree à fcrn et leurs procedes d'utilisation</sb> |
US20100021472A1 (en) * | 2008-07-25 | 2010-01-28 | Geetha Srikrishna | Methods for diagnosing and treating cancer |
WO2010019553A2 (fr) | 2008-08-11 | 2010-02-18 | Banyan Biomarkers, Inc. | Procédé de détection de biomarqueurs et test d'état neurologique |
WO2010021415A1 (fr) | 2008-08-18 | 2010-02-25 | Seoul National University Industry Foundation | Procédé pour la lutte contre la métastase cancéreuse ou la migration de cellules cancéreuses par modulation du taux cellulaire de lysyl-arnt synthétase |
WO2010061393A1 (fr) | 2008-11-30 | 2010-06-03 | Compugen Ltd. | Séquences d'acides aminés et de nucléotides de variants de he4 et leurs procédés d'utilisation |
CA2743707A1 (fr) | 2008-12-04 | 2010-06-10 | Pioneer Hi-Bred International, Inc. | Procedes et compositions pour un rendement ameliore par une expression ciblee de knotted1 |
EP2865689A1 (fr) | 2008-12-08 | 2015-04-29 | Compugen Ltd. | FAM26F polypeptides et polynucléotides, et leurs utilisations en tant que médicament cible pour produire des médicaments et des agents biologiques |
US20100291100A1 (en) * | 2009-03-27 | 2010-11-18 | Gojo Industries, Inc. | Compositions And Methods For Screening And Using Compounds Antagonizing Spore-Surface Interactions |
GB2470939A (en) | 2009-06-10 | 2010-12-15 | Dna Supernova Ltd | Signal amplification microspheres |
US9493834B2 (en) | 2009-07-29 | 2016-11-15 | Pharnext | Method for detecting a panel of biomarkers |
EP2485762B1 (fr) | 2009-10-11 | 2017-12-13 | Biogen MA Inc. | Tests associés à un anti-vla-4 |
US9428586B2 (en) | 2009-12-01 | 2016-08-30 | Compugen Ltd | Heparanase splice variant |
AU2011203815B2 (en) | 2010-01-11 | 2015-11-26 | Biogen Ma Inc. | Assay for JC virus antibodies |
US11287423B2 (en) | 2010-01-11 | 2022-03-29 | Biogen Ma Inc. | Assay for JC virus antibodies |
EP2531224B1 (fr) | 2010-01-26 | 2019-06-05 | Bioregency, Inc. | Compositions et procédés associés à l'argininosuccinate synthétase |
CN102740976B (zh) | 2010-01-29 | 2016-04-20 | 精密公司 | 取样-应答微流体盒 |
TWI518325B (zh) | 2010-02-04 | 2016-01-21 | 自治醫科大學 | 對alk抑制劑具有先抗性或後抗性癌症的識別、判斷和治療 |
WO2011106738A2 (fr) | 2010-02-25 | 2011-09-01 | Fred Hutchinson Cancer Research Center | Utilisation de clonotypes tcr en tant que biomarqueurs de maladie |
EP2544688B1 (fr) | 2010-03-02 | 2016-09-07 | President and Fellows of Harvard College | Procédés et compositions pour le traitement du syndrome d'angelman |
US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
CN107098958B (zh) | 2010-03-26 | 2021-11-05 | 达特茅斯大学理事会 | Vista调节性t细胞介体蛋白、vista结合剂及其用途 |
US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
WO2011156715A2 (fr) | 2010-06-10 | 2011-12-15 | The Regents Of The University Of Michigan | Méthodes de traitement de troubles métaboliques et de maladies cardiovasculaires |
EP3327035A1 (fr) | 2010-06-22 | 2018-05-30 | Precision Biologics Inc. | Antigènes et anticorps spécifiques des cancers du côlon et du pancréas |
US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
WO2012028697A1 (fr) | 2010-09-01 | 2012-03-08 | Eth Zürich, Institute Of Molecular Biology And Biophysics | Système de purification par affinité sur la base d'une complémentation de brin de donneur |
US8999335B2 (en) | 2010-09-17 | 2015-04-07 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
US9068014B2 (en) | 2010-09-23 | 2015-06-30 | Precision Biologics, Inc. | Colon and pancreas cancer peptidomimetics |
EP2477032A1 (fr) | 2011-01-18 | 2012-07-18 | Baxter International Inc | Mesure d'anticorps anti-amyloïdes dans le sang humain |
JP2014507649A (ja) | 2011-01-18 | 2014-03-27 | バクスター・インターナショナル・インコーポレイテッド | ヒト血液中の抗βアミロイド抗体の測定 |
AU2012239961A1 (en) | 2011-04-08 | 2013-10-24 | Biogen Ma Inc. | Biomarkers predictive of therapeutic responsiveness to IFNbeta and uses thereof |
CN105601741A (zh) | 2011-04-15 | 2016-05-25 | 卡姆普根有限公司 | 多肽和多核苷酸及其用于治疗免疫相关失调和癌症的用途 |
KR102046666B1 (ko) | 2011-05-25 | 2019-11-19 | 이나뜨 파르마 | 염증성 장애의 치료를 위한 항-kir 항체 |
KR20140147797A (ko) | 2011-06-27 | 2014-12-30 | 더 잭슨 래보라토리 | 암 및 자가면역 질환의 치료 방법 및 조성물 |
AU2012277376B2 (en) | 2011-06-30 | 2016-11-24 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
US9835621B2 (en) | 2011-07-14 | 2017-12-05 | University Of Kentucky Research Foundation | Process for detection of alzheimer's disease from a serum sample |
AU2012298884B2 (en) | 2011-08-23 | 2017-11-16 | Foundation Medicine, Inc. | Novel KIF5B-RET fusion molecules and uses thereof |
WO2013043012A2 (fr) * | 2011-09-22 | 2013-03-28 | Medicinal Bioconvergence Research Center | Nouvelle utilisation de la leucyle arnt synthétase |
EP2802417B1 (fr) | 2012-01-09 | 2019-05-15 | Micronics, Inc. | Système de réacteur microfluidique |
EP2807271B1 (fr) | 2012-01-24 | 2018-08-22 | CD Diagnostics, Inc. | Système de détection d'une infection dans le liquide synovial |
CN104185681A (zh) | 2012-02-01 | 2014-12-03 | 卡姆普根有限公司 | C1orf32抗体及其用于治疗癌症的用途 |
KR101353930B1 (ko) | 2012-02-20 | 2014-01-27 | 주식회사 나노엔텍 | 신규한 항원의 검출방법 및 그를 이용한 장치 |
US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
EP2864352B1 (fr) | 2012-06-22 | 2018-08-08 | The Trustees Of Dartmouth College | Nouveaux produits de recombinaison vista-ig et leur utilisation dans le traitement des troubles autoimmuns, allergiques et inflammatoires |
CA3163776A1 (fr) | 2012-08-03 | 2014-02-06 | Foundation Medicine, Inc. | Papillomavirus humain en tant que predicteur du pronostic du cancer |
CA2884704C (fr) | 2012-09-07 | 2023-04-04 | Randolph J. Noelle | Modulateurs vista de diagnostic et de traitement de cancer |
WO2014043633A1 (fr) | 2012-09-17 | 2014-03-20 | Agios Pharmaceuticals, Inc. | Utilisation de e-cadhérine et de vimentine pour la sélection de patients répondant à un traitement |
JP6348115B2 (ja) | 2012-10-26 | 2018-06-27 | ザ ユニバーシティー オブ クイーンズランド | がん療法のためのエンドサイトーシス阻害剤および抗体の使用 |
US20150299803A1 (en) | 2012-11-05 | 2015-10-22 | Pronai Therapeutics, Inc. | Methods of Using Biomarkers for the Treatment of Cancer by Modulation of BCL2 Expression |
WO2014071358A2 (fr) | 2012-11-05 | 2014-05-08 | Foundation Medicine, Inc. | Nouvelles molécules de fusion de ntrk1 et leurs utilisations |
ES2761951T3 (es) | 2012-11-21 | 2020-05-21 | Agios Pharmaceuticals Inc | Inhibidores de glutaminasa y métodos de uso |
WO2014079011A1 (fr) | 2012-11-22 | 2014-05-30 | Agios Pharmaceuticals, Inc. | Composés hétérocycliques pour inhiber la glutaminase et procédés d'utilisation de ceux-ci |
WO2014100732A1 (fr) | 2012-12-21 | 2014-06-26 | Micronics, Inc. | Circuits fluidiques et procédés de fabrication associés |
EP3549674B1 (fr) | 2012-12-21 | 2020-08-12 | PerkinElmer Health Sciences, Inc. | Films à faible élasticité pour utilisation micro-fluidique |
KR20150097764A (ko) | 2012-12-21 | 2015-08-26 | 마이크로닉스 인코포레이티드. | 휴대형 형광 검출 시스템 및 미량분석 카트리지 |
US9938344B2 (en) | 2012-12-28 | 2018-04-10 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
CA2898326C (fr) | 2013-01-18 | 2022-05-17 | Foundation Medicine, Inc. | Methodes de traitement du cholangiocarcinome |
JP2016515534A (ja) | 2013-03-15 | 2016-05-30 | ヴェロ バイオ,エルエルシー | 子癇症及び子癇前症を治療するための方法 |
CN105228641A (zh) | 2013-03-21 | 2016-01-06 | 密歇根大学董事会 | 治疗代谢紊乱的方法 |
US10246708B2 (en) | 2013-05-06 | 2019-04-02 | Alnylam Pharmaceuticals, Inc. | Dosages and methods for delivering lipid formulated nucleic acid molecules |
US10386377B2 (en) | 2013-05-07 | 2019-08-20 | Micronics, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
WO2014182847A1 (fr) | 2013-05-07 | 2014-11-13 | Micronics, Inc. | Dispositif pour la préparation et l'analyse d'acides nucléiques |
WO2014182831A1 (fr) | 2013-05-07 | 2014-11-13 | Micronics, Inc. | Procédés de préparation d'échantillons d'acides nucléiques faisant appel à des minéraux argileux et à des solutions alcalines |
WO2014193804A1 (fr) | 2013-05-28 | 2014-12-04 | Biogen Idec Ma Inc. | Méthodes d'évaluation de risque de développement d'une lemp |
US9861633B2 (en) | 2013-07-17 | 2018-01-09 | Foundation Medicine, Inc. | Methods of treating urothelial carcinoma |
WO2015050959A1 (fr) | 2013-10-01 | 2015-04-09 | Yale University | Anticorps anti-kits et leurs méthodes d'utilisation |
WO2015063604A2 (fr) | 2013-11-01 | 2015-05-07 | Imberti Luisa | Biomarqueurs prédictifs de la réponse thérapeutique à ifnβ et utilisations de ceux-ci |
US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
MX369173B (es) | 2013-12-24 | 2019-10-30 | Janssen Pharmaceutica Nv | Anticuerpos y fragmentos anti-vista. |
WO2015131078A1 (fr) | 2014-02-27 | 2015-09-03 | Biogen Ma Inc. | Procédé d'évaluation du risque de lemp |
BR112016021620A2 (pt) | 2014-03-21 | 2018-07-10 | Agios Pharmaceuticals Inc | compostos e seus métodos de uso |
WO2015172083A1 (fr) | 2014-05-08 | 2015-11-12 | Biogen Ma Inc. | Diméthylfumarate et promédicaments pour le traitement de la sclérose en plaques |
US20170269075A1 (en) | 2014-05-12 | 2017-09-21 | Biogen Ma Inc. | Biomarkers predictive of lupus progression and uses thereof |
CN107073109B (zh) | 2014-06-11 | 2021-08-06 | 凯西·A·格林 | Vista激动剂和拮抗剂抑制或增强体液免疫的用途 |
WO2016026978A1 (fr) | 2014-08-22 | 2016-02-25 | Universite Nice Sophia Antipolis | Méthodes et compositions pharmaceutiques pour le traitement de la toxicomanie |
CA2963935A1 (fr) | 2014-10-08 | 2016-04-14 | Novartis Ag | Biomarqueurs predictifs de la reactivite therapeutique a une therapie par recepteurs antigeniques chimeres et leurs utilisations |
WO2016090347A1 (fr) | 2014-12-05 | 2016-06-09 | Immunext, Inc. | Identification de vsig8 en tant que récepteur putatif de vista et son utilisation pour produire des modulateurs de vista/vsig8 |
US11279768B1 (en) | 2015-04-03 | 2022-03-22 | Precision Biologics, Inc. | Anti-cancer antibodies, combination therapies, and uses thereof |
BR112017027870A2 (pt) | 2015-06-24 | 2018-08-28 | Janssen Pharmaceutica Nv | anticorpos e fragmentos anti-vista |
CN108780084B (zh) | 2015-09-03 | 2022-07-22 | 诺华股份有限公司 | 预测细胞因子释放综合征的生物标志物 |
BR112018016461A2 (pt) | 2016-02-12 | 2019-10-01 | Janssen Pharmaceutica Nv | anticorpos e fragmentos anti-vista, usos dos mesmos e métodos de identificação dos mesmos |
US11725247B2 (en) | 2016-02-29 | 2023-08-15 | Foundation Medicine, Inc. | Methods of treating cancer |
KR20170108203A (ko) | 2016-03-16 | 2017-09-27 | 주식회사 피플바이오 | 응집형-형성 폴리펩타이드의 응집형을 검출하는 방법 |
MX2018012469A (es) | 2016-04-15 | 2019-07-04 | Immunext Inc | Anticuerpos vista antihumanos y uso de los mismos. |
US11832801B2 (en) | 2016-07-11 | 2023-12-05 | Arizona Board Of Regents On Behalf Of Arizona State University | Sweat as a biofluid for analysis and disease identification |
WO2018045162A1 (fr) | 2016-09-01 | 2018-03-08 | Biogen Ma Inc. | Biomarqueurs prédictifs de la sclérose en plaques progressive primaire et leurs utilisations |
WO2019237119A1 (fr) | 2018-06-08 | 2019-12-12 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Nouvelles compositions et procédés de détection d'une infection par onchocerca volvulus |
AU2019310040A1 (en) | 2018-07-23 | 2021-02-11 | Enclear Therapies, Inc. | Methods of treating neurological disorders |
WO2020023417A1 (fr) | 2018-07-23 | 2020-01-30 | Enclear Therapies, Inc. | Méthodes de traitement de troubles neurologiques |
EP3853378A4 (fr) | 2018-09-21 | 2022-05-11 | President and Fellows of Harvard College | Méthodes et compositions pour le traitement du diabète, et méthodes pour l'enrichissement en un arnm codant pour des protéines sécrétées |
JP7225713B2 (ja) * | 2018-11-09 | 2023-02-21 | 東洋紡株式会社 | 抗ストレプトリジンo測定用ラテックス粒子の製造方法 |
AU2020271894A1 (en) | 2019-04-11 | 2021-12-02 | Enclear Therapies, Inc. | Methods of amelioration of cerebrospinal fluid and devices and systems therefor |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1130581A (en) * | 1965-01-01 | 1968-10-16 | Gevaert Photo Prod Nv | Photographic gelatin compositions containing colour couplers |
GB1247688A (en) * | 1968-02-26 | 1971-09-29 | Agfa Gevaert | Monomeric and polymeric 2-pyrazoline-5-one colour couplers |
GB1269355A (en) * | 1968-07-18 | 1972-04-06 | Agfa Gevaert A Naamlooze Venno | 0-aryl-2-pyrazoline-5-one colour couplers |
EP0032270A1 (fr) * | 1980-01-11 | 1981-07-22 | Akzo N.V. | Application de colorants hydrophobes, dispersables dans l'eau, comme marqueurs dans des essais immunologiques |
US4340664A (en) * | 1979-10-15 | 1982-07-20 | Agfa-Gevaert, N.V. | Copolymer latex and photographic silver halide materials containing such latex |
US4369226A (en) * | 1979-03-19 | 1983-01-18 | California Institute Of Technology | Polyglutaraldehyde synthesis and protein bonding substrates |
US4419453A (en) * | 1981-09-28 | 1983-12-06 | The Dow Chemical Company | Immunological agglutination assays with dyed or colored latex and kits |
WO1984003358A1 (fr) * | 1983-02-25 | 1984-08-30 | Covalent Technology Corp | Surfaces insolubles traitees pour inhiber la liaison d'une proteine non-specifique |
EP0154749A1 (fr) * | 1984-02-14 | 1985-09-18 | Becton Dickinson and Company | Immunoessai en phase solide avec lecture visuelle |
EP0170746A1 (fr) * | 1984-08-07 | 1986-02-12 | Covalent Technology Corporation | Essai pour matières à activité biologique |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3163625A (en) * | 1960-04-13 | 1964-12-29 | Du Pont | Color-forming monomers and polymers of acrylic acid amides of 3-aminopyrazolone |
CH485782A (de) * | 1964-06-23 | 1970-02-15 | Gevaert Photo Prod Nv | Verfahren zur Emulsionspolymerisation |
GB1363230A (en) * | 1970-12-16 | 1974-08-14 | Agfa Gevaert | Colour couplers and their use in colour photography |
GB1453057A (en) * | 1973-02-26 | 1976-10-20 | Agfa Gevaert | Polymeric colour forming and competing couplers |
JPS5975152A (ja) * | 1982-10-23 | 1984-04-27 | Tatsuo Suzuta | 螢光免疫ラテツクス粒子 |
US4745075A (en) * | 1984-09-06 | 1988-05-17 | Burroughs Wellcome Co. | Diagnostic test methods |
-
1986
- 1986-12-04 CA CA000524512A patent/CA1291031C/fr not_active Expired - Lifetime
- 1986-12-10 DE DE8686202231T patent/DE3688184T2/de not_active Expired - Lifetime
- 1986-12-10 EP EP86202231A patent/EP0227173B1/fr not_active Expired - Lifetime
- 1986-12-10 AT AT86202231T patent/ATE87743T1/de not_active IP Right Cessation
- 1986-12-10 ES ES86202231T patent/ES2054617T3/es not_active Expired - Lifetime
- 1986-12-15 US US06/941,446 patent/US4837168A/en not_active Expired - Lifetime
- 1986-12-23 JP JP61305543A patent/JP2509201B2/ja not_active Expired - Lifetime
-
1994
- 1994-05-16 US US08/243,425 patent/US5498551A/en not_active Expired - Lifetime
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1130581A (en) * | 1965-01-01 | 1968-10-16 | Gevaert Photo Prod Nv | Photographic gelatin compositions containing colour couplers |
GB1247688A (en) * | 1968-02-26 | 1971-09-29 | Agfa Gevaert | Monomeric and polymeric 2-pyrazoline-5-one colour couplers |
GB1269355A (en) * | 1968-07-18 | 1972-04-06 | Agfa Gevaert A Naamlooze Venno | 0-aryl-2-pyrazoline-5-one colour couplers |
US4369226A (en) * | 1979-03-19 | 1983-01-18 | California Institute Of Technology | Polyglutaraldehyde synthesis and protein bonding substrates |
US4340664A (en) * | 1979-10-15 | 1982-07-20 | Agfa-Gevaert, N.V. | Copolymer latex and photographic silver halide materials containing such latex |
EP0032270A1 (fr) * | 1980-01-11 | 1981-07-22 | Akzo N.V. | Application de colorants hydrophobes, dispersables dans l'eau, comme marqueurs dans des essais immunologiques |
US4419453A (en) * | 1981-09-28 | 1983-12-06 | The Dow Chemical Company | Immunological agglutination assays with dyed or colored latex and kits |
WO1984003358A1 (fr) * | 1983-02-25 | 1984-08-30 | Covalent Technology Corp | Surfaces insolubles traitees pour inhiber la liaison d'une proteine non-specifique |
EP0154749A1 (fr) * | 1984-02-14 | 1985-09-18 | Becton Dickinson and Company | Immunoessai en phase solide avec lecture visuelle |
EP0170746A1 (fr) * | 1984-08-07 | 1986-02-12 | Covalent Technology Corporation | Essai pour matières à activité biologique |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4997772A (en) * | 1987-09-18 | 1991-03-05 | Eastman Kodak Company | Water-insoluble particle and immunoreactive reagent, analytical elements and methods of use |
GB2215047A (en) * | 1988-02-01 | 1989-09-13 | Boehringer Biochemia Srl | Analytical method using biospecific reagents labelled with colored macromolecular structures |
AU625455B2 (en) * | 1988-02-23 | 1992-07-09 | Teikoku Hormone Mfg. Co., Ltd. | Simple method for immunological assay |
AU635716B2 (en) * | 1988-09-23 | 1993-04-01 | Abbott Laboratories | Indicator reagents, diagnostic assays and test kits employing organic polymer latex particles |
EP0360088A3 (fr) * | 1988-09-23 | 1991-01-16 | Abbott Laboratories | Réactifs indicateurs, essais diagnostiques et trousses de réactifs utilisant les particules organiques de latex polymère |
EP0360088A2 (fr) * | 1988-09-23 | 1990-03-28 | Abbott Laboratories | Réactifs indicateurs, essais diagnostiques et trousses de réactifs utilisant les particules organiques de latex polymère |
WO1991001485A1 (fr) * | 1989-07-19 | 1991-02-07 | Seradyn, Inc. | Methode d'analyse et appareil |
WO1992004045A1 (fr) * | 1990-08-31 | 1992-03-19 | Warner-Lambert Company | Nouveaux antagonistes de cholecystokinine, preparation et utilisation therapeutique de ces composes |
US5266497A (en) * | 1990-08-31 | 1993-11-30 | Japan Synthetic Rubber Co., Ltd. | Immunochromatographic assay with improved colored latex |
FR2673292A1 (fr) * | 1991-02-26 | 1992-08-28 | Sebia Sa | Procede d'immunofixation ou d'immunoelectrophorese a l'aide d'un ensemble d'au moins deux immunserums differents ou deux solutions d'immunoglobulines differentes et kit pour la mise en óoeuvre d'un tel procede. |
WO1992020746A1 (fr) * | 1991-05-14 | 1992-11-26 | Hybritech, Incorporated | Compositions polymeres a anticorps lies |
BE1006245A3 (fr) * | 1993-05-03 | 1994-06-14 | Ape Associates As | Reactifs pour la detection ou le dosage d'un analyte dans un echantillon, trousses les contenant, et procede de detection ou de dosage utilisant ces reactifs. |
EP0623822A1 (fr) * | 1993-05-03 | 1994-11-09 | Ape Associates S.A. | Réactifs indicateurs pour la détection ou le dosage d'un analyte, trousses les contenant, et procédé de détection ou de dosage |
AU2008289857B2 (en) * | 2007-08-23 | 2014-06-05 | Phc Corporation | Use of non-specific reaction inhibitor |
WO2018132062A1 (fr) * | 2017-01-12 | 2018-07-19 | Agency For Science, Technology And Research | Procédé de détection de la présence de différents analytes cibles et kits associés |
Also Published As
Publication number | Publication date |
---|---|
EP0227173B1 (fr) | 1993-03-31 |
ES2054617T3 (es) | 1994-08-16 |
DE3688184D1 (de) | 1993-05-06 |
DE3688184T2 (de) | 1993-07-08 |
US5498551A (en) | 1996-03-12 |
EP0227173A3 (en) | 1989-08-02 |
ATE87743T1 (de) | 1993-04-15 |
US4837168A (en) | 1989-06-06 |
JPS62195556A (ja) | 1987-08-28 |
JP2509201B2 (ja) | 1996-06-19 |
CA1291031C (fr) | 1991-10-22 |
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